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The conditions are found under which the frequency of a new gene altering the recombination fraction between two loci controlling meiotic drive will increase. When the model mimics the recombination reducing effects of a chromosomal rearrangement, such as an inversion or duplication, then the result is that the frequency of the chromosomal rearrangement in the population will increase. This may help explain the presence of inversions and duplications (or insertions) in the segregation-distorter system in Drosophila. In some cases it is found that if the new gene causes any alteration in the recombination fraction between the two loci, the frequency of the gene will increase.

In the analysis of recombination inAspergillus nidulanscoincidence values of about 1 are found in 3-point tests using markers more than a few map units apart. In comparable tests in which the marked intervals were very short (0·1 map unit or less), coincidence values of over 100 had been found. To account for this difference it was proposed that a necessary condition for recombination, termed ‘effective pairing’, was realized at any particular point on the chromosome in only a small fraction of a population of cells at meiosis. It was supposed that when effective pairing occurred it extended over a very short segment of the chromosome and that the probability of recombination in the effectively paired segment was high, i.e. about 1. Coincidence values greater than unity would be a necessary consequence of such a situation provided the intervals in question had a total length not much greater than that of effective pairing segments.The experiments described in this paper were undertaken in an attempt to measure the mean length of effectively paired segments, their distribution, and the frequency of exchange within them. The data suggest a mean length of about 0·4 map unit, a mean exchange frequency of about 0·6, and a distribution which is variable, perhaps random.The occurrence of localized negative interference suggests a way in which a number of difficulties encountered in relating the experimental evidence concerning the time and mechanism of recombination with the cytological evidence concerning the sequence of events at meiosis might be resolved. The data indicate that the frequency of recombination between linked loci is a measure principally of the frequency of effective pairing between them. If effective pairing is synonymous with homologous contact between chromosomes, and evidence is presented which suggests this may be the case, it becomes possible to construct a simple model which is compatible with the view that recombination takes place before chromosomes are paired, in the cytologically observable sense (i.e. before zygotene), at meiosis.The recombination events occurring within effectively paired regions are generally, although possibly not exclusively, reciprocal. Non-reciprocal recombinants have been encountered inAspergillusand other organisms, characterized by the occurrence of 3:1 ratios in tetrads. On the basis of evidence currently available it does not seem necessary to invoke a special mechanism of recombination, distinct from crossing over, to account for the formation of non-reciprocal recombinaiits. A single mechanism of recombination of the copy-choice type which, although primarily a reciprocal process, is nevertheless not necessarily exactly so or always so in detail, will account for the observed results.

A B S T R A C T The gene rec-l+ which reduces allelic recombination at the his-I locus by a factor of between 15 and 30 has no effect upon allelic recombination at the his-2, his-3, his-5, his-6 and his-7 loci. Other genes controlling recombination at two of these loci, namely rec-x at his-2 and rec-w at his8, have been found. There is a strong possibility that rec-x may be identical with rec-3, so far known to regulate recombination only at the am-i locus. It is probable that the stocks used all carry a rec+ gene which regulates recombination at the his8- locus, since all prototroph frequencies are -low, but no regulatory gene active at the his-5 and his-7 loci. THE DISCOVERY of genes which regulate recombination at specific loci (D.G. Catcheside, 1968) and the inability, to discover any other effect of them (D.E.A. Catcheside, 1968a, b) has prompted intensification of the search for further specific loci sensitive to a given rec gene. The possibility that a given rec gene might somehow be in control of several genes concerned with the specification of the enzymes in a biosynthetic pathway has been examined with particular reference to rec-1 and all but one of the his loci in Neurospora crassa; his-4 could not be studied owing to technical difficulties. Such a relationship to his genes could arise if a prime function of the rec-l+ gene was to produce a regulator of transcription, able to act on several of the genes in the histidine pathway, the regulation of recombination being secondary. The rec-1 and rec-l+ genes are assayed by measuring the frequency of recombination between two his-i alleles, usually K83 and K651, one of the stocks (the tester) being known to be rec-1. In the presence of rec-l+ the frequency of prototrophs produced by crosses of these two alleles is about 1 per 105; in the absence of rec-l+ the frequency is about 30 per 105. A particular difficulty attends the study of a possible effect on other his loci, since recombination at any one his locus cannot be studied in the presence in the same stocks of a mutant at another his locus. It has been necessary, therefore, to locate rec-1 and then proceed to insert rec-1 and rec-1+ into various stocks of other his mutants by breeding methods in which the rec-1 segment was defined and followed by means of two genes, one on each side of the rec-1 locus.

It has been shown that intragenic mitotic recombinants in the pfp gene in Aspergillus nidulans derive both by a reciprocal and a non-reciprocal process. Reciprocal recombination usually modifies the genes in both the strands involved; on the other hand non-reciprocal recombination does not modify the gene.

T-007 strain of Drosophila melanogaster is known to show recombination in males. The present study established the following points: (1) Clustering occurrence of recombinant, unequal recovery of complementary products of recombination, relatively high frequency of recombination around centromeric region, and relatively frequent occurrence of mosaic phenontype flies—all of these seem to indicate that a considerable fraction of male recombination in the T-007 strain is of premeiotic, or somatic origin, although a fraction still could be of meiotic origin; (2) Male recombination occurs in the third as well as in the second chromosomes, and the frequencies of recombinations are comparable between these two chromosome pairs.

A second chromosome of Drosophila melanogaster (symbol T-007 ) isolated from a natural population in Harlingen, Texas, was found to undergo recombination in heterozygous males. Heterozygous males transmit this chromosome with a frequency, k , of about 0.4, considerably reduced from the expected value of 0.5. The frequency of male recombination and the k value are negatively correlated, indicating that the two phenomena are in some way related. The complementary recombinant products are recovered in equal frequency and the recombination is not restricted to the heterochromatic regions. The time of recombination is not certain, but the distribution of recombinants is more suggestive of meiotic than of premeiotic occurrence. In the natural population of these flies, the frequency of chromosomes with male recombination is 20% or more.

Diploid cells of the yeast Saccharomyces cerevisiae become committed to recombination at meiotic levels without becoming committed to the meiotic disjunction of chromosomes. These two events of the meiotic process can be separated by removing cells from a meiosis-inducing medium and returning them to a medium that promotes vegetative cell division. Cells removed at an appropriate time remain diploid, revert to mitosis, and display recombination with meiotic-like frequencies. Those removed after this time are committed to the completion of meiosis. Diploids of three conditional sporulation-deficient mutants ( spo 1-1, spo 2-1, and spo 3-1) have been examined for recombination at restrictive temperatures. All exhibit commitment to recombination without commitment to meiotic disjunction as in the wild type. Cells of spo 1-1/ spo 1-1 do not replicate the spindle pole body for meiosis I; thus, recombination ability can be acquired by cells that do not proceed beyond this cytological stage.

Publisher Summary The essential characteristics of meiosis are pairing, crossing over, and reduction in chromosome number. Fertilization and meiosis are compensating events; a failure of one or the other causes a breakdown in the orderly system of sexual reproduction. The invention of meiosis has led to evolutionary consequences of the first order of magnitude. Independent assortment of the members of different pairs of chromosomes results in genotypic diversity because gametes are produced with random combinations of nonhomologous chromosomes from the two parental gametes. Additional genotypic diversity among the sexual cells arises from crossing over or recombination of segments between the two homologous chromosomes of each bivalent. This ceaseless shuffling and recombination of chromosomes and chromosomal segments afford the organism a mechanism by which myriad constellations of genes are formed. Those best adapted to the environment would survive, while the others perish. Therefore, recombination makes it possible for the organism to exploit its potential genic plasticity. At varying stages during development of organisms with gametic or sporic meiosis, a group or groups of cells are set aside, which are destined to undergo meiosis.

Publisher Summary This chapter discusses that study on genetic recombination in phage T4 shows the participating DNA molecules are broken and rejoined during the process. It appears, likely, that breakage and rejoining may account for all recombination, as the extent of breakage, as measured by physical methods, is in rather good agreement with the extent of exchange, as measured by genetic methods. In genetic crosses, there are on the average 20 exchanges per genome and these are apparently clustered to some extent. Isotope transfer experiments indicate that there is a bimodal distribution of parental DNA; progeny particles, which receive any parental label, receive on the average 5–10%, or less than 1% of a chromosomal equivalent. The chapter explores that the joining of parental fragments occurs in several steps, which are mediated by specific enzymes. In intermediate structures, complementary sections of different parental origin are held together by hydrogen bonds involved in base pairing. Subsequently, the parental fragments become covalently linked. Physically hybrid regions in base-paired structures may be genetically heterozygous. They become homozygous only after the hybrid DNA is replicated or repaired. Average recombination frequencies per unit length DNA are higher in T4 crosses than in most other systems. One map unit corresponds to 100–200 nucleotide pairs, both according to physical and genetic measurements. However, the average recombination frequency per unit length DNA is not equal over the entire T4 genome.

IT has been generally accepted that recombination in a chromosome segment adjacent to a heterozygous inversion is reduced, often to an extreme degree, as compared with recombination in the same segment in homozygous normal controls. This generalization is based for the most part upon the behavior of such segments observed in females of Drosophila (e.g., STURTEVANT and BEADLE 1936; DOBZHANSKY and EPLING 1948) and upon the a priori consideration that the synaptic difficulties introduced by the inversion should lead to reduced frequencies of exchange, particularly near the break points of the inversion. RHOADES and DEMPSEY (1953) have reported a case in maize, and cited earlier reports of two other cases in the same organism (MORGAN 1950; RUSSELL and BURNHAM 1950), in which regions adjacent to heterozygous inversions showed a recombination frequency as much as fourfold higher than the standard map or control recombination values. RHOADES and DEMPSEY seemed to regard this as a real difference in the behavior of the chromosomes of Drosophila and maize, and briefly discussed possible reasons for this difference. One may note, however, that ALEXANDER (1952) has also reported a 50 percent increase in recombination in a region adjacent to the Plum2 inversion in Drosophila melanogaster. It has occurred to the writer that the normal operation of interference W inversion heterozygotes should, in some cases, result in an observed recombination frequency (measured in zygotes) in such an adjacent region which was higher than the actual frequency of recombination at meiosis. The basis of this effect is, essentially, a tendency toward the selective elimination from the zygotic population of chromatids which are nonrecombinant in the adjacent segment. This paper describes the functioning of the mechanism operating to produce this effect, develops means of estimating the magnitude of the effect in the various kinds of situations which may be encountered, and demonstrates that only a part of the observed difference between maize and Drosophila may be explained by the effect.

In Drosophila melanogaster the recessive 3rd chromosome gene, mei-1, reduces recombination in the region around ct (target region) in the X chromosome drastically. Other regions show less extreme reductions or increased recombination (centromere region). Totally, recombination frequency in X is halved. Recombination in autosomes is little affected by mei-1. Coincidence appears unaffected by mei-1, at least in X. Nondisjunction of X's in females is trebled by mei-1. — Interchromosomal effects of the Cy inversions increase recombination in X. In the target region, the effects of Cy and of mei-1 are additive. Both X-rays and EMS reduce recombination in this region. The reduction is additive to mei-1 effects. According to Sandler et al. (1968) genes changing recombination but not coincidence probably affect the exchange process rather than its preconditions. However this need not be the case for each such gene. By analogy to probability, different factors with additive effects on a phenomenon are likely to affect the same process. In the target region, mei-1, Cy, X-rays and EMS may therefore all affect the same process, presumably chromosome pairing.

T is now well established that recombination can occur between allelic mutants I of independent origin. Allelic recombination differs, however, from classical crossing over in that it is frequently nonreciprocal and has a lower than expected correlation with the exchange of outside markers. The relationship of nonreciprocal to reciprocal recombination is not yet understood (cf. ROMAN 1963). Models have been suggested which ascribe different mechanisms to the two types of recombination (STADLER 1959; ST. LAWRENCE 1959), or a common mechanism to both (FREESE 1957; PRITCHARD 1960). In either case, it is generally thought that nonreciprocal recombination is the result of an interaction between DNA molecules at a time when replication is occurring. The present study deals with allelic recombination in diploid yeast cells undergoing sporulation. It had previously been shown (ROMAN 1956) that the frequency of allelic recombination rises sharply during meiosis compared with the frequency in mitotically dividing cells, In theory, there should be one cycle of DNA replication during meiosis of yeast. It was our purpose to see if we could determine the period of replication and to find if this period could be correlated with the time of occurrence of allelic recombination.

Recent studies in the fungi, particularly Neurospora and Schizophyllum, have revealed a number of genetic features which, viewed in conjunction with earlier observations on other organisms, form a pattern, or model, which appears to be basic to the control of recombination in all eukaryotes, including higher organisms. It is assumed that the control is exercised on mechanisms that produce new alleles through recombination, as understood in broad terms and including such a likely phenomenon as gene conversion, which may or may not involve crossing-over, as well as equal and unequal crossing-over. The recombination may thus occur between alleles in either the homozygous or heterozygous condition. In the model, regulatory genes and breeding behaviour are integrated into one self-regulatory system controlling the production of new genetic variation. The model is based on the following five general features, largely substantiated by the results in Neurospora and Schizophyllum: 1) The frequency of recombination in a particular chromosomal region is controlled by specific regulatory genes (rec). 2) There may be a number of such specific, regulatory genes responsible for recombination in a given region. 3) A rec. locus may influence recombination in more than one region. 4) The regulatory genes have no specific physical relationship with the region(s) they control, and are usually located at random in the genome. 5) Of the allelic forms of the regulatory genes it is always the dominant gene which suppresses recombination and the recessive gene which increases recombination. The rec system is epistatic to other genetic elements jointly involved in the overall control of recombination in a specific region. It is suggested that usually the control of recombination in a given region is exercised, cumulatively, by the balance of the dominant and recessive genes of the specific rec loci in the organism. Outbreeding, with the associated high heterozygosity of the regulatory rec loci, virtually “switches off” recombination, producing few new variations. Inbreeding produces homozygosity of these loci, resulting in certain individuals which will have a considerable number of their regulatory loci in the homozygous recessive condition and in which recombination will be “switched on”, producing new variation at a high frequency. Inbreeding is thus an integrated, evolutionary system of considerable importance, and is not a degenerate “dead end”, as many investigators have previously thought. The model has another compensatory function in evolution. In major loci, or in an operon, where there are structural genes and closely linked operator genes, as exemplified by the S locus, there are indications that the present model is concerned with the regulation of both structural and operator genes. The consequences of the model in the two classes of genes, however, are in direct contrast to each other: High heterozygosity which is instrumental in switching “off” recombination, and which is therefore helpful in maintaining stability in the structural gene, is conducive to functional variation of the operator gene; and high homozygosity, which is instrumental in switching “on” recombination, and which is therefore helpful in producing variation in the structural gene, is conducive to the stability of the operator gene. This model of the control of genetic variation in a specific chromosomal region is significant in development as well as in evolution, and throws light on a number of hitherto “intractable” problems peculiar to the higher organisms. For example, the model is helpful in explaining: 1) the origin of new self-incompatibility alleles in the flowering plants; 2) the impressive speciation in the waif flora (and fauna) of the oceanic islands; 3) the presence of high genetic variability in inbreeding species of plants; 4) environmentally-induced heritable variation in certain plants; and 5) the genetic mechanism of antibody diversity in animals.

The yield of prototrophic recombinants in crosses between nit-2 alleles is repressed in the presence of the rec-z+ gene. Similarly, recombination between his-I alleles is repressed by the rec-I+ gene. Experiments reported in this paper show that if the rec-I+ and rec-z+ loci are different, the worst estimate indicates that they are located not more than O� 67 map units apart with 95 % probability. It is likely, therefore, that rec-I controls the frequency of recombination between nit-2 alleles as well as between his-I alleles. This is in line with evidence that each of the genes rec-2+ and rec-3+ repress recombination in more than one chromosomal segment. Nevertheless, each rec gene is specific in its action, repressing recombination in only a limited fraction of the genome.

Two different recombination genes each control both allelic recombination and non-allelic recombination at a number of well-defined places in the genome of N. crassa. The dominant gene rec-3+ reduces allelic recombination at the am-l and his-2loci and in the segment between sn and his-2. The dominant gene rec-2+ reduces allelic recombination at the his-3 locus and in the three separate segments pyr-3 his-5, his-3 ad-3, and arg-3 sn. It is possible that rec-l+, which reduces allelic recombination at the his-l locus, also reduces non-allelic recombination between his-2 and his-3. The identity of rec-x with rec-3 is very highly probable; the identity of rec-w with rec-2 is also highly probable.